THE ROLE OF LUBRICANTS IN SOLID ORAL DOSAGE MANUFACTURING

by: John C Carter, Carter Pharmaceutical Consulting, Inc.
© 2001 -2006. All Rights Reserved

All solid oral dosage products consist of an “active” ingredient or drug. It is rare to find a solid oral dosage product consisting of drug alone. To produce a final product that is not only practical and convenient to handle but also facilitates patient compliance, the drug substance needs to be processed with other excipients. These drug “fillers” or excipients serve many roles in the formulation. Some examples are binders, fillers (or diluents), disintegrants, colorants, buffering agents and coatings. One class of functional excipients that are essential in most solid oral dosage forms is “lubricants”.

WHAT ARE “LUBRICANTS”?

Lubricants are agents added in small quantities to tablet and capsule formulations to improve certain processing characteristics.

. There are three roles identified with lubricants as follows:

1.
True Lubricant Role:
  To decrease friction at the interface between a tablet’s surface and the die wall during ejection and reduce wear on punches & dies.
2.
Anti-adherent Role:
  Prevent sticking to punch faces or in the case of encapsulation, lubricants
prevent sticking to machine dosators, tamping pins, etc
3.
Glidant Role:
  Enhance product flow by reducing interparticulate friction.

     .
II.  Properties of a Good Lubricant:          

1.
Low Shear Strength- Want the lubricant to hear during blending, not the granules or other excipients in the formulation.
2.
Able to form a “durable layer” over the surface covered.
3.
Non-Toxic
4.
Chemically Inert
5.
Unaffected by Process Variables
6.
Posses Minimal Adverse Effects on the Finished Dosage Form.     

          
III.  There are two major types of lubricants:

1.
Hydrophilic
  Generally poor lubricants, no glidant or anti-adherent properties.
2.
Hydrophobic
  Most widely used lubricants in use today are of the hydrophobic category. Hydrophobic lubricants are generally good lubricants and are usually effective at relatively low concentrations. Many also have both anti- adherent and glidant properties. For these reasons, hydrophobic lubricants are used much more frequently than hydrophilic compounds.

Most  tableting materials require lubrication to some degree. Only a few drugs and excipients do not require lubrication ie. ASA, starch & microcrystalline cellulose.  But these are exceptions. 

Of all the lubricants in use, “magnesium stearate” is the most widely used lubricant in the pharmaceutical industry. Although it is used in low concentrations, it is often the cause of many problems experienced in solid oral dosage forms.

Determining the level of lubricants to use and the manner in which they are incorporated into a batch is critical. If concentrations are too low, or distribution and mixing times are inadequate, problems can arise. 

Some examples are as follows: 

  • Punch filming
  • Picking
  • Sticking
  • Capping
  • Binding in the die cavity


If concentrations are too high, or distribution and mixing times are too great, potential problems include:

  • Decrease in tablet hardness
  • Inability to compress into tablets
  • Increase in tablet disintegration times (DTs)
  • Decrease in rate of dissolution

 

HOW DO LUBRICANTS WORK?

Magnesium Stearate:

Magnesium (and calcium) stearate exists as “plate-like” crystals (or lamellae) stacked together like a deck of cards. As the blending process proceeds, plates continue to shear off and coat adjacent particles of granules, drug or other excipients. The higher the concentration of Magnesium Stearate used or the longer this blending continues, the more complete this coating of the adjacent particles will become.For effective lubrication, you do not need and, in fact, you do not want to coat everything too completely with the lubricant or the problems mentioned previously are likely to occur. 

What causes these problems?

The hydrophobic coating interferes with “wetting” thereby leading to increases in the time required for the tablet to disintegrate and/or the drug to become dissolved.

Additionally, a complete coating of lubricant may affect tablet hardness by interfering with the interparticle bonding required by formulations where tablets are formed with components that bond by plastic deformation.

Tablets formed by brittle fracture are less affected because brittle fracture produces clean “unlubricated” sites where bonding can occur during compression.

Wet granulation formulations are also less affected (than direct compression formulations) since significant clean surfaces are formed during compression as the granules deform with shear to provide bonding sites.

The use of Magnesium Stearate as a lubricant has further complications in that a variety of commercial samples have been known to exhibit significant batch-to-batch variation in their lubricant properties. Three factors have been determined to be mainly responsible for this variation:

1.
Differences in chemical composition:
  Commercial Magnesium Stearate actually consists of a mixture of several different fatty acids. A composition consisting of Magnesium Stearate to palmitate in a ratio of 25% to 75% respectively is thought to be optimum for “lubricity” and shear properties. But this composition s not usually found in commercial samples.
   
2.
Differences in specific surface area:
  Since the lubricating properties of magnesium stearate are related to its ability to coat other particles in a formulation during mixing, samples of a greater surface area should be able to do this more effectively. There is some argument about this however, since it is known that the surface area of magnesium stearate continually changes during blending as a result of its delamination.
   
3.
Differences in crystal structure:
  Different crystalline structures have different strengths of attraction between adjacent lamellae thereby affecting its relative ability to delaminate and subsequently coat adjacent particles.

 

EXCIPIENTS USED AS LUBRICANTS, ANTIADHERANT, or GLIDANTS:

LUBRICANTS:

 

Magnesium Stearate (and Calcium Stearate):

Water Solubility: Insoluble
Conc. Use Range: 0.25 - 1.5% 

Magnesium stearate is the most commonly used and most effective of all lubricants. It is also the most likely to cause compression & dissolution problems. Concentration, grade and mixing parameters must be carefully controlled. These stearates are alkaline in reaction and cannot be used with some acidic drugs like ASA. Magnesium stearate has good glidant and anti-adherent properties.

   
  Stearic Acid:
 
Water Solubility: Insoluble
Conc. Use Range:1 - 4%
 
Not as effective a lubricant as Magnesium Stearate. Mixing times not as critical. Incompatibilities include some alkaline salts such as sodium saccharin and sodium phenobarbital.
   
  Hydrogenated Vegetable Oil (Sterotex, Lubritab, Cutina):
 
Water Solubility: Insoluble
Conc. Use Range: 2 - 5%
 
Solid at room temperature, these materials melt at compression pressures and temperatures to impart a lubricating effect.
   
 

Mineral Oil:
 
Water Solubility: Insoluble
Conc. Use Range:  1 - 3% 

Light mineral oil is an efficient lubricant. But since it must be finely sprayed onto granules and powders to be used, it also can cause noticeable mottling or spotting on tablet surfaces. For these reasons, it is not commonly used anymore. But can still be found in some formulations.

   
 

Polyethylene Glycol 4000 -6000 (PEG):
 
Water Solubility: Soluble
Conc. Use Range: 2 - 5%

Has been used as a water-soluble lubricant for some water soluble and effervescent tablet formulations. Fairly high concentration and low particle size needed to be moderately effective as a lubricant. It has no glidant or anti-adherent properties.

   
 

Sodium Lauryl Sulfate (SLS):
 
Water Solubility: Soluble
Conc. Use Range:  2 - 3% 

Effective at reducing ejection forces but does not help much for sticking to punch faces. Therefore, it must be used in conjunction with an anti-adherent.


OTHER LUBRICANTS:     

 

Glyceryl Palmitostearate (Precirol) & Glyceryl Behenate (Compitrol 888):

Water Solubility: Insoluble
Conc. Use Range: 2 - 5%  

   
 

Sodium Benzoate:

Water Solubility: Soluble   

Conc. Use Range: 1 - 4%

   
 

Sodium Stearyl Fumarate (Pruv): 

Water Solubility: Soluble
Conc. Use Range: 0.5 - 2%

 

ANTIADHERANTS & GLIDANTS:
   

 

Talc:

Water Solubility: Insoluble
Conc. Use Range: 1-10%

Not particularly effective on its own as a tablet lubricant or glidant. But very effective with lubricants in the role of an anti-adherent in that it effectively prevents sticking to surfaces. When using talc, it should always be blended into the formulation first followed by the lubricant (i.e. magnesium stearate). 

   
 

Fumed Silicon Dioxide (Cab-o-sil):

Water Solubility:       Insoluble
Conc. Use Range: As anti-adherent, 1-2% As glidant, 0.1 - 0.5%

Fumed Silicon Dioxide has no lubricant properties. It is commercially available as very fine particles (approx. 0.014 microns), which tend to agglomerate into “balls”.
It functions by coating granules, etc. and reducing interparticulate friction of these thereby improving flow characteristics. For processing, this material must be screened into a batch. However, due to the extremely fine particle size, it should be pre-blended with another component to facilitate screening and distribution. It is an extremely effective glidant at low concentrations, and has anti-adherent properties at higher concentrations. However at higher concentrations, flow characteristics may actually be impeded resulting in an increase in weight variation.   

 
Unfortunately the “ideal” lubricant for use in all occasions and with all formulations does not yet exist. However, by understanding how this important class of Excipients functions is solid oral dosage manufacturing, lubricants can be made to work for you and not against you.